Krystal 2010.

Methods	Randomised, parallel group, controlled trial
Participants	Insomnia diagnosis criteria (method of diagnosis): DSM‐IV‐TR primary diagnosis of insomnia Other diagnoses: not stated Number of participants randomised: n = 240 Doxepin 1 mg: n = 77 Doxepin 3 mg: n = 82 Number of participants: n = 214 Doxepin 1 mg: n = 70 Doxepin 3 mg: n = 74 Age, mean (SD) years: 71.4 (5.2) Doxepin 1 mg: 71.3 (5.2) Doxepin 3 mg: 71.4 (4.9) Placebo: 71.5 (5.5) Gender (M/F): 35%/65% Doxepin 1 mg: 35%/65% Doxepin 3 mg: 30%/70% Race/ethnicity: 80% white; 9% African‐American; 9% Hispanic; 2% other Doxepin 1 mg: 82% white; 6% African‐American; 10% Hispanic; 1% other Doxepin 3 mg: 77% white; 12% African‐American; 11% Hispanic; 1% other Placebo: 83% white; 7% African‐American; 5% Hispanic; 5% other Country: USA Setting: multicentre study in 31 sleep centres Included: aged > 65 years; insomnia (DSM‐IV‐TR and sleep diaries) > 3 months, PSG LPS > 10 min, wake time during sleep ≥ 60 min and TST > 240 and ≤ 390 Excluded: excessive use of alcohol, nicotine or caffeinated beverages (no measurement given); intentional napping > twice a week; variation in bedtime; use of hypnotic medication or other medication that affects sleep; ≥ 15 apnoea/hypopnoea events per hr Withdrawals: Doxepin 1 mg: 7‐9% (1% adverse event, 3% protocol violation, 4% non‐compliance, 1% other) Doxepin 3 mg: 8‐10% (4% adverse event, 2% consent withdrawn, 1% protocol violation, 2% other) Placebo: 11‐14% (4% adverse effect; 7% consent withdrawn; 2% protocol violation) Baseline imbalances: slight gender imbalances across 3 groups
Interventions	Intervention: doxepin 1 mg and 2 mg; night‐time administration of drug 30 min prior to bed time; supervised in the laboratory on study nights or self‐administered at home. Administered for 12 weeks Comparator: placebo; night‐time administration of drug 30 min prior to bed time; supervised in the laboratory on study nights or self‐administered at home. Administered for 12 weeks. 1 week of single‐blind placebo administration to all eligible participants prior to treatment phase
Outcomes	Primary outcomes Subjective ratings of LSO, TST and sleep quality ISI PGI scale of sleep, 5‐item rating Secondary outcomes EEG data reported for WASO, TST, SE% last quarter of the night, NAW and LPS Measures of next‐day psychomotor functioning, subjective next‐day alertness or drowsiness Adverse effects
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation done by an external person/group, but no details given
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Reported double blind, but no further details
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Reported double blind, but no further details
Incomplete outcome data (attrition bias) All outcomes	High risk	26/240 participants did not complete the study (Pg 1555, "study population"). No imputation for ITT analysis
Selective reporting (reporting bias)	Unclear risk	Some self‐report data that were not available at baseline were imputed.
Other bias	High risk	Study funded by a pharmaceutical company and authors salaries were paid by the same company.